Metabolic disorder and functional disturbance in the central executive network in minimal hepatic encephalopathy.

The aim of this paper is to investigate dynamical functional disturbance in central executive network in minimal hepatic encephalopathy and determine its association with metabolic disorder and cognitive impairment. Data of magnetic resonance spectroscopy and resting-state functional magnetic resonance imaging were obtained from 27 cirrhotic patients without minimal hepatic encephalopathy, 20 minimal hepatic encephalopathy patients, and 24 healthy controls. Central executive network was identified utilizing seed-based correlation approach. Dynamic functional connectivity across central executive network was calculated using sliding-window approach. Functional states were estimated by K-means clustering. Right dorsolateral prefrontal cortex metabolite ratios (i.e. glutamate and glutamine complex/total creatine, myo-inositol / total creatine, and choline / total creatine) were determined. Neurocognitive performance was determined by psychometric hepatic encephalopathy scores. Minimal hepatic encephalopathy patients had decreased myo-inositol / total creatine and choline / total creatine and increased glutamate and glutamine complex / total creatine in right dorsolateral prefrontal cortex (all P ≤ 0.020); decreased static functional connectivity between bilateral dorsolateral prefrontal cortex and between right dorsolateral prefrontal cortex and lateral-inferior temporal cortex (P ≤ 0.001); increased frequency and mean dwell time in state-1 (P ≤ 0.001), which exhibited weakest functional connectivity. Central executive network dynamic functional indices were significantly correlated with right dorsolateral prefrontal cortex metabolic indices and psychometric hepatic encephalopathy scores. Right dorsolateral prefrontal cortex myo-inositol / total creatine and mean dwell time in state-1 yielded best potential for diagnosing minimal hepatic encephalopathy. Dynamic functional disturbance in central executive network may contribute to neurocognitive impairment and could be correlated with metabolic disorder.

The Future of Molecular Studies through the Lens of Large Language Models.

The rapid advancement of large language models is reshaping research across various fields, offering a novel approach to the complex realm of molecular studies. Our evaluation of GPT-4 and GPT-3.5, focusing on their performance in generating and optimizing molecular structures, highlights GPT-4's strengths in certain aspects of molecular optimization. However, it also revealed challenges in accurately creating complex molecules. Addressing these issues, we propose possible directions for future molecular science research. These suggestions aim to forge new paths for exploring the intricacies of molecular structures, potentially bringing new efficiencies and innovations in the field.

KEYNOTE-033: Randomized phase 3 study of pembrolizumab vs docetaxel in previously treated, PD-L1-positive, advanced NSCLC.

KEYNOTE-033 (NCT02864394) was a multicountry, open-label, phase 3 study that compared pembrolizumab vs docetaxel in previously treated, programmed death-ligand 1 (PD-L1)-positive, advanced non-small cell lung cancer (NSCLC), with most patients enrolled in mainland China. Eligible patients were randomized (1:1) to pembrolizumab 2 mg/kg or docetaxel 75 mg/m2 every 3 weeks. Primary endpoints were overall survival (OS) and progression-free survival and were evaluated sequentially using stratified log-rank tests, first in patients with PD-L1 tumor proportion score (TPS) ≥50% and then in patients with PD-L1 TPS ≥1% (significance threshold: P < .025, one-sided). A total of 425 patients were randomized to pembrolizumab (N = 213) or docetaxel (N = 212) between 8 September 2016 and 17 October 2018. In patients with a PD-L1 TPS ≥50% (n = 227), median OS was 12.3 months with pembrolizumab and 10.9 months with docetaxel; the hazard ratio (HR) was 0.83 (95% confidence interval [CI]: 0.61-1.14; P = .1276). Because the significance threshold was not met, sequential testing of OS and PFS was ceased. In patients with a PD-L1 TPS ≥1%, the HR for OS for pembrolizumab vs docetaxel was 0.75 (95% CI: 0.60-0.95). In patients from mainland China (n = 311) with a PD-L1 TPS ≥1%, HR for OS was 0.68 (95% CI: 0.51-0.89). Incidence of grade 3 to 5 treatment-related AEs was 11.3% with pembrolizumab vs 47.5% with docetaxel. In summary, pembrolizumab improved OS vs docetaxel in previously treated, PD-L1-positive NSCLC without unexpected safety signals; although the statistical significance threshold was not reached, the numerical improvement is consistent with that previously observed for pembrolizumab in previously treated, advanced NSCLC.

White matter microstructural disruption in minimal hepatic encephalopathy: a neurite orientation dispersion and density imaging (NODDI) study.

PURPOSE: To evaluate the ability of neurite orientation dispersion and density imaging (NODDI) for detecting white matter (WM) microstructural abnormalities in minimal hepatic encephalopathy (MHE). METHODS: Diffusion-weighted images, enabling the estimation of NODDI and diffusion tensor imaging (DTI) parameters, were acquired from 20 healthy controls (HC), 22 cirrhotic patients without MHE (NHE), and 15 cirrhotic patients with MHE. Tract-based spatial statistics were used to determine differences in DTI (including fractional anisotropy [FA] and mean/axial/radial diffusivity [MD/AD/RD]) and NODDI parameters (including neurite density index [NDI], orientation dispersion index [ODI], and isotropic volume fraction [ISO]). Voxel-wise analyses of correlations between diffusion parameters and neurocognitive performance determined by Psychometric Hepatic Encephalopathy Score (PHES) were completed. RESULTS: MHE patients had extensive NDI reduction and rare ODI reduction, primarily involving the genu and body of corpus callosum and the bilateral frontal lobe, corona radiata, external capsule, anterior limb of internal capsule, temporal lobe, posterior thalamic radiation, and brainstem. The extent of NDI and ODI reduction expanded from NHE to MHE. In both MHE and NHE groups, the extent of NDI change was quite larger than that of FA change. No significant intergroup difference in ISO/MD/AD/RD was observed. Tissue specificity afforded by NODDI revealed the underpinning of FA reduction in MHE. The NDI in left frontal lobe was significantly correlated with PHES. CONCLUSION: MHE is characterized by diffuse WM microstructural impairment (especially neurite density reduction). NODDI can improve the detection of WM microstructural impairments in MHE and provides more precise information about MHE-related pathology than DTI.

scDeepSort: a pre-trained cell-type annotation method for single-cell transcriptomics using deep learning with a weighted graph neural network.

Advances in single-cell RNA sequencing (scRNA-seq) have furthered the simultaneous classification of thousands of cells in a single assay based on transcriptome profiling. In most analysis protocols, single-cell type annotation relies on marker genes or RNA-seq profiles, resulting in poor extrapolation. Still, the accurate cell-type annotation for single-cell transcriptomic data remains a great challenge. Here, we introduce scDeepSort (https://github.com/ZJUFanLab/scDeepSort), a pre-trained cell-type annotation tool for single-cell transcriptomics that uses a deep learning model with a weighted graph neural network (GNN). Using human and mouse scRNA-seq data resources, we demonstrate the high performance and robustness of scDeepSort in labeling 764 741 cells involving 56 human and 32 mouse tissues. Significantly, scDeepSort outperformed other known methods in annotating 76 external test datasets, reaching an 83.79% accuracy across 265 489 cells in humans and mice. Moreover, we demonstrate the universality of scDeepSort using more challenging datasets and using references from different scRNA-seq technology. Above all, scDeepSort is the first attempt to annotate cell types of scRNA-seq data with a pre-trained GNN model, which can realize the accurate cell-type annotation without additional references, i.e. markers or RNA-seq profiles.

Altered dynamic brain activity and its association with memory decline after night shift-related sleep deprivation in nurses.

AIMS AND OBJECTIVES: To investigate, for the first time, aberrant time-varying local brain activity in nurses following night shift-related sleep deprivation (SD) and its association with memory decline. BACKGROUND: Prior studies have elucidated alterations in static local brain activity resulting from SD in the occupations outside medical profession. DESIGN: A longitudinal study followed the STROBE recommendations. METHODS: Twenty female nurses underwent resting-state functional magnetic resonance imaging and memory function assessment (by Complex Figure Test (CFT) and the California Verbal Learning Test, Second Edition (CVLT-II)) twice, once in a rested wakefulness (RW) state and another after SD. By combining the sliding-window approach and amplitude of low-frequency fluctuation (ALFF) analysis, the dynamic ALFF (dALFF) variability was calculated to reflect the characteristics of dynamic local brain activity. RESULTS: Poor performance on the CFT and CVLT-II was observed in nurses with night shift-related SD. Reduced dALFF variability was found in a set of cognition-related brain regions (including the medial/middle/superior frontal gyrus, anterior/posterior cingulate gyrus, precuneus, angular gyrus, orbitofrontal and subgenual areas, and posterior cerebellum lobe), while increased dALFF variability was observed in the somatosensory-related, visual and auditory regions. SD-related dALFF variability alterations correlated with changes in subjects' performance on the CFT and CVLT-II. CONCLUSIONS: Night shift-related SD disturbed dynamic brain activity in high cognitive regions and induced compensatory reactions in primary perceptual cortex. Identifying dALFF variability abnormalities may broaden our understanding of neural substrates underlying SD-related cognitive alterations, especially memory dysfunction. RELEVANCE TO CLINICAL PRACTICE: Night shift-related SD is as an important occupational hazard affecting brain function in nurses. The effective countermeasure addressing the adverse outcomes of SD should be advocated for nurses. PATIENT OR PUBLIC CONTRIBUTION: Patients or public were not involved in the design and implementation of the study or the analysis and interpretation of the data.

Clinicopathological features and resistance mechanisms in HIP1-ALK-rearranged lung cancer: A multicenter study.

Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) respond well to ALK tyrosine kinase inhibitors (TKIs), and echinoderm microtubule-associated protein-like 4 (EML4)-ALK-rearranged NSCLC accounts for the majority of those patients. However, few studies have evaluated ALK-TKIs treatment for patients with huntingtin-interacting protein 1 (HIP1)-ALK fusions. This retrospective study evaluated the clinicopathological characteristics, genomic features, response to ALK-TKIs, and resistance mechanisms in 11 cases with HIP1-ALK fusions from five Chinese centers. Patients who received crizotinib at the Chinese centers had an objective response rate of 90% [9/10 cases, 95% confident index (CI): 54.1%-99.5%], median progression-free survival of 17.9 months (95% CI: 5.8-NA months), and median overall survival of 58.8 months (95% CI: 24.7-NA months). One patient who received first-line lorlatinib treatment achieved partial response for > 26.5 months. Despite the small sample size, HIP1-ALK (H21:A20) variant was the most common variant (four of 11 cases, 36.4%) and associated with better outcomes. Among the 11 cases, there were eight patients having available specimens for genetic testing before ALK-TKIs treatment and four patients undergoing biopsy after ALK-TKIs failure. The most common coexisting gene was TP53 among 11 patients and two of four patients after crizotinib failure harbored acquired ALK mutations (e.g., L1152V/Q1146K and L1196M). Brigatinib treatment appeared to be effective for a patient who failed crizotinib treatment because of the L1152V/Q1146K mutations, which might be related to increased binding affinity to these mutants. Although HIP1-ALK-rearranged NSCLC appears to initially respond well to ALK-TKIs, crizotinib resistance may be correlated with the AKAP9-BRAF fusion, ALK compound mutations (L1152V/Q1146K), and the ALK L1196M mutation. Larger studies are needed to evaluate the significance of HIP1-ALK-rearranged NSCLC.

Subsequent treatments beyond progression on osimertinib in EGFR-mutated NSCLC and leptomeningeal metastases.

BACKGROUND: Despite the reported efficacy of osimertinib, central nervous system (CNS) progression is still frequent in EGFR-mutated NSCLC. This study aimed to reveal site-specific resistant mechanisms to osimertinib and investigate subsequent treatments for leptomeningeal metastases (LM). METHODS: EGFR-mutated NSCLC with LM who progressed on osimertinib were included. Molecular analysis of cerebrospinal fluid (CSF) at osimertinib progression was performed. Subsequent treatments of LM were collected and analyzed. RESULTS: A total of 246 patients were identified. Only those with LM as a progression site on osimertinib were included (n=81). In 58 CSF-plasma pairs, more alterations were uniquely detected in CSF (77%) than in plasma (7%). These mechanisms led to 22 patients receiving matched targeted therapy. Among them, 16 (72.7%) had a clinical response. The median overall survival was 7.2 months. For non-matched therapy (n=59), the osimertinib combination had a longer median overall survival than the regimen switch in CNS-only progression (15.3 vs. 7 months, p=0.03). Finally, serial monitoring by CSF revealed the potential evolution of LM. CONCLUSIONS: Private resistant mechanisms in CSF might match osimertinib-resistant LM for targeted therapy. Besides, continuing osimertinib with intensification strategy might prolong survival, especially for those with CNS-only progression. Prospective  exploration is needed.

Phase I/Ib dose-escalation study of avelumab in Chinese patients with advanced solid tumors.

Aim: Data for avelumab (anti-PD-L1 antibody) in Chinese patients are limited. Patients & methods: Phase I/Ib, open-label, dose-escalation study of Chinese patients with advanced solid tumors. Primary study objectives were to evaluate the maximum tolerated dose (MTD) and pharmacokinetics (PK) of avelumab. Results: 24 patients received avelumab 3 mg/kg every 2 weeks (Q2W; n = 3), 10 mg/kg Q2W (n = 7), 20 mg/kg Q2W (n = 6) or 10 mg/kg weekly for 12 weeks and then Q2W thereafter (n = 8). MTD was not reached. Avelumab exposure was increased in higher dose groups. Partial responses occurred in two patients (confirmed in one patient); best overall response was stable disease in nine patients. Conclusion: Data for avelumab in Chinese patients with advanced solid tumors were consistent with previous global studies.

Avelumab is a form of medicine that falls under the category of immunotherapy. This means that it can help the immune system find and destroy cancer cells. In this study, researchers looked at the safety of avelumab in a small group of Chinese people with different types of cancer. Researchers also looked at blood levels of avelumab after treatment. Different doses of avelumab were given to different groups of people. Overall, study results for avelumab in Chinese people were similar to results from earlier studies in other countries.  Clinical trial registration: NCT03523390 (ClinicalTrials.gov).

Dynamic Changes in Functional Network Connectivity Involving Amyotrophic Lateral Sclerosis and Its Correlation With Disease Severity.

BACKGROUND: Aberrant static functional connectivity (FC) has been well demonstrated in amyotrophic lateral sclerosis (ALS); however, ALS-related alterations in FC dynamic properties remain unclear, although dynamic FC analyses contribute to uncover mechanisms underlying neurodegenerative disorders. PURPOSE: To explore dynamic functional network connectivity (dFNC) in ALS and its correlation with disease severity. STUDY TYPE: Prospective. SUBJECTS: Thirty-two ALS patients and 45 healthy controls. FIELD STRENGTH/SEQUENCE: Multiband resting-state functional images using gradient echo echo-planar imaging and T1-weighted images were acquired at 3.0 T. ASSESSMENT: Disease severity was evaluated with the revised ALS Functional Rating Scale (ALSFRS-R) and patients were stratified according to diagnostic category. Independent component analysis was conducted to identify the components of seven intrinsic brain networks (ie, visual/sensorimotor (SMN)/auditory/cognitive-control (CCN)/default-mode (DMN)/subcortical/cerebellar networks). A sliding-window correlation approach was used to compute dFNC. FNC states were determined by k-mean clustering, and state-specific FNC and dynamic indices (fraction time/mean dwell time/transition number) were calculated. STATISTICAL TESTS: Two-sample t test used for comparisons on dynamic measures and Spearman's correlation analysis. RESULTS: ALS patients showed increased FNC between DMN-SMN in state 1 and between CCN-SMN in state 4. Patients remained in state 2 (showing the weakest FNC) for a significantly longer time (mean dwell time: 49.8 ± 40.1 vs. 93.6 ± 126.3; P < 0.05) and remained in state 1 (showing a relatively strong FNC) for a shorter time (fraction time: 0.27 ± 0.25 vs. 0.13 ± 0.20; P < 0.05). ALS patients exhibited less temporal variability in their FNC (transition number: 10.2 ± 4.4 vs. 7.8 ± 3.8; P < 0.05). A significant correlation was observed between ALSFRS-R and mean dwell time in state 2 (r = -0.414, P < 0.05) and transition number (r = 0.452, P < 0.05). No significant between-subgroup difference in dFNC properties was found (all P > 0.05). DATA CONCLUSION: Our findings suggest aberrant dFNC properties in ALS, which is associated with disease severity. LEVEL OF EVIDENCE: 2 TECHNICAL EFFICACY: Stage 3.

Abnormal cerebral microstructures revealed by diffusion kurtosis imaging in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease in which cerebral structural impairment is a consistent feature. PURPOSE: To investigate cerebral microstructural changes in ALS using diffusion kurtosis imaging (DKI) for the first time. STUDY TYPE: Prospective. SUBJECTS: Eighteen ALS patients and 20 healthy controls. FIELD STRENGTH/SEQUENCE: DKI images were obtained by a spin-echo echo-planar imaging sequence on a 3T MRI scanner, with three b-values (0, 1000, and 2000 s/mm2 ) and 64 diffusion encoding directions. ASSESSMENT: The revised ALS Functional Rating Scale (ALSFRS-R) was administered to assess disease severity, and the symptom duration and disease progression rate were also recorded. Voxel-based analysis was applied to examine the alteration of DKI metrics (ie, mean kurtosis metrics [MK], axial kurtosis [AK], and radial kurtosis [RK]) and the conventional diffusion metrics (ie, fractional anisotropy, mean diffusivity, axial diffusivity, and radial diffusivity). STATISTICAL TESTS: Student's t-test, chi-square test, and Pearson correlation analysis. RESULTS: ALS patients showed MK reductions in gray matter areas, including the bilateral precentral gyrus, bilateral paracentral lobule, and left anterior cingulate gyrus; they also showed decreased MK values in white matter (WM) in the bilateral precentral gyrus, bilateral corona radiata, bilateral middle corpus callosum, left occipital lobe, and right superior parietal lobule. The spatial distribution of the regions with reduced RK was similar to those with decreased MK. No significant AK difference was found between groups. The correlation analysis revealed significant associations between DKI metrics and clinical assessments such as ALSFRS-R score and disease duration. Additionally, several WM regions showed between-group differences in conventional diffusion metrics; but the spatial extent was smaller than that with reduced DKI metrics. DATA CONCLUSION: The reduction in DKI metrics indicates decreased microstructural complexity in ALS, involving both motor-related areas and extramotor regions. DKI metrics can serve as potential biomarkers for assessing disease severity. LEVEL OF EVIDENCE: 2 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2020;51:554-562.

Reduced Cortical Complexity in Cirrhotic Patients with Minimal Hepatic Encephalopathy.

Purpose: Gray matter volume loss, regional cortical thinning, and local gyrification index alteration have been documented in minimal hepatic encephalopathy (MHE). Fractal dimension (FD), another morphological parameter, has been widely used to describe structural complexity alterations in neurological or psychiatric disease. Here, we conducted the first study to investigate FD alterations in MHE. Methods and Materials: We performed high-resolution structural magnetic resonance imaging on cirrhotic patients with MHE (n = 20) and healthy controls (n = 21). We evaluated their cognitive performance using the psychometric hepatic encephalopathy score (PHES). The regional FD value was calculated by Computational Anatomy Toolbox (CAT12) and compared between groups. We further estimated the association between patients' cognitive performance and FD values. Results: MHE patients presented significantly decreased FD values in the left precuneus, left supramarginal gyrus, right caudal anterior cingulate cortex, right isthmus cingulate cortex, right insula, bilateral pericalcarine cortex, and bilateral paracentral cortex compared to normal controls. In addition, the FD values in the right isthmus cingulate cortex and right insula were shown to be positively correlated with patients' cognitive performance. Conclusion: Aberrant cortical complexity is an additional characteristic of MHE, and FD analysis may provide novel insight into the neurobiological basis of cognitive dysfunction in MHE.

Optomechanical transistor: controlling the optical bistability in a photonic molecule.

We theoretically investigate the optical bistability in a composite photonic molecule cavity optomechanical system consisting of two whispering gallery mode microcavities, where one of the optical cavities is optomechanical with a high quality factor, and the other optical cavity is an auxiliary cavity with high cavity dissipation. By controlling the coupling strength J between the two cavities determined by their distance, the decay rate ratio δ of the two cavities, and the pump power P, the optical bistability can be controlled. Further, the transmission spectrum of the signal field can be efficiently attenuated or amplified, depending on the power of a second "gating" (pump) field P, and other parameters. Our study for photonic-molecule optomechanics systems may be a promising candidate for single-photon transistors and pave the way for potential applications in quantum information technologies.

Hippocampal atrophy and functional connectivity disruption in cirrhotic patients with minimal hepatic encephalopathy.

The hippocampus is a crucial pathological node for minimal hepatic encephalopathy (MHE) and it is associated with various cognitive impairments. Investigations on alterations involving hippocampal morphology and functional connectivity (FC) in MHE are limited. This study aimed to simultaneously evaluate hippocampal volume and FC alterations and their association with cognitive decline in MHE. Twenty-two cirrhotic patients with MHE, 31 cirrhotic patients without MHE (NHE), and 43 healthy controls underwent high-resolution T1-weighted imaging, resting-state functional magnetic resonance imaging, and cognition assessment based on Psychometric Hepatic Encephalopathy Score (PHES). The structural images were preprocessed using a voxel-based morphometry method, during which hippocampal volume was measured. The hippocampal connectivity network was identified using seed-based correlation analysis. Hippocampal volume and FC strength were compared across the three groups and correlated against the PHES results of the cirrhotic patients. Compared to the controls, MHE patients exhibited a significantly lower bilateral hippocampal volume. A slight decrease in hippocampal volume was obtained from NHE to MHE, but it did not reach statistically significance. In addition, the average FC strength of the bilateral hippocampal connectivity network was significantly lower in the MHE patients. In particular, the MHE patients showed a decrease in FC involving the left hippocampus to bilateral posterior cingulate gyrus and left angular gyrus. The MHE patients also showed FC reduction between the right hippocampus and bilateral medial frontal cortex. A progressive reduction in hippocampal FC from NHE to MHE was also observed. The bilateral hippocampal FC strength (but not hippocampal volume) was positively correlated with the PHES results of the cirrhotic patients. Our assessment of MHE patients revealed decreased hippocampal volume, which suggests regional atrophy, and reduced hippocampal connectivity with regions that are primarily involved in the default-mode network, thereby suggesting a functional disconnection syndrome. These alterations reveal the mechanisms underlying cognitive deterioration with disease progression.

Focus shaping of the radially polarized Laguerre-Gaussian-correlated Schell-model vortex beams.

In this paper, we introduce a new kind of partially coherent vector beam with special correlation function and vortex phase named radially polarized Laguerre-Gaussian-correlated Schell-model (LGCSM) vortex beam as a natural extension of scalar LGCSM vortex beam. The realizability conditions for such beam are derived. The tight focusing properties of a radially polarized LGCSM vortex beam passing through a high numerical aperture (NA) objective lens are investigated numerically based on the vectorial diffraction theory. We find that not only the transverse component but also the longitudinal component of the focal field distributions can be shaped by regulating the structures of the correlation functions, which is quite different from that of the conventional radially polarized partially coherent beam. Moreover, a series of wildly used focal field with novel structure, e.g., focal spot, flat-topped or doughnut beam profiles, needle-like focal field and controllable three-dimensional (3D) optical cage, were obtained. These results indicate that the focus shaping can be achieved by combining the regulation of the structures of the correlation functions with the regulation of beam parameters effectively. Our results may be useful for potential applications in optical trapping, optical high-resolution microscopy and optical data storage.

Crizotinib in advanced non-small-cell lung cancer with concomitant ALK rearrangement and c-Met overexpression.

OBJECTIVE: Crizotinib can target against mesenchymal-epithelial transition (MET) and anaplastic lymphoma kinase (ALK), which has been considered as a multi-targeted tyrosine kinase inhibitor (TKI). The objective of this study was to explore the efficacy of crizotinib in advanced non-small-cell lung cancer (NSCLC) with concomitant ALK rearrangement and c-Met overexpression. METHODS: Totally, 4622 advanced NSCLC patients from two institutes (3762 patients at the Guangdong Lung Cancer Institute from January 2011 to December 2016 and 860 cases at the Perking Cancer Hospital from January 2015 to December 2016) were screened for ALK rearrangement with any method of IHC, RACE-coupled PCR or FISH. C-Met expression was performed by IHC in ALK-rearranged patients, and more than 50% of cells with high staining were defined as c-Met overexpression. The efficacy of crizotinib was explored in the ALK-rearranged patients with or without c-Met overexpression. RESULTS: Sixteen patients were identified with c-Met overexpression in 160 ALK-rearranged cases, with the incidence of 10.0% (16/160). A total of 116 ALK-rearranged patients received the treatment of crizotinib. Objective response rate (ORR) was 86.7% (13/15) in ALK-rearranged patients with c-Met overexpression and 59.4% (60/101)in those without c-Met overexpression, P = 0.041. Median PFS showed a trend of superiority in c-Met overexpression group (15.2 versus 11.0 months, P = 0.263). Median overall survival (OS) showed a significant difference for ALK-rearranged patients with c-Met overexpression group of 33.5 months with the hazard ratio (HR) of 3.2. CONCLUSIONS: C-Met overexpression co-exists with ALK rearrangement in a small population of advanced NSCLC. There may be a trend of favorable efficacy of crizotinib in such co-altered patients.

Disrupted topological organization of brain structural network associated with prior overt hepatic encephalopathy in cirrhotic patients.

OBJECTIVES: To investigate structural brain connectome alterations in cirrhotic patients with prior overt hepatic encephalopathy (OHE). METHODS: Seventeen cirrhotic patients with prior OHE (prior-OHE), 18 cirrhotic patients without prior OHE (non-prior-OHE) and 18 healthy controls (HC) underwent diffusion tensor imaging. Neurocognitive functioning was assessed with Psychometric Hepatic Encephalopathy Score (PHES). Using a probabilistic fibre tracking approach, we depicted the whole-brain structural network as a connectivity matrix of 90 regions (derived from the Automated Anatomic Labeling atlas). Graph theory-based analyses were performed to analyse topological properties of the brain network. RESULTS: The analysis of variance showed significant group effects on several topological properties, including network strength, global efficiency and local efficiency. A progressive decrease trend for these metrics was found from non-prior-OHE to prior-OHE, compared with HC. Among the three groups, the regions with altered nodal efficiency were mainly distributed in the frontal and occipital cortices, paralimbic system and subcortical regions. The topological metrics, such as network strength and global efficiency, were correlated with PHES among cirrhotic patients. CONCLUSIONS: The cirrhotic patients developed structural brain connectome alterations; this is aggravated by prior OHE episode. Disrupted topological organization of the brain structural network may account for cognitive impairments related to prior OHE. KEY POINTS: • Altered structural brain connectome is found in cirrhotic patients. • Structural brain connectome alterations could be aggravated by prior-OHE episode. • Altered structural brain connectome may account for cognitive impairments associated with prior OHE.

Tailoring the Interfacial Chemical Interaction for High-Efficiency Perovskite Solar Cells.

The ionic nature of perovskite photovoltaic materials makes it easy to form various chemical interactions with different functional groups. Here, we demonstrate that interfacial chemical interactions are a critical factor in determining the optoelectronic properties of perovskite solar cells. By depositing different self-assembled monolayers (SAMs), we introduce different functional groups onto the SnO2 surface to form various chemical interactions with the perovskite layer. It is observed that the perovskite solar cell device performance shows an opposite trend to that of the energy level alignment theory, which shows that chemical interactions are the predominant factor governing the interfacial optoelectronic properties. Further analysis verifies that proper interfacial interactions can significantly reduce trap state density and facilitate the interfacial charge transfer. Through use of the 4-pyridinecarboxylic acid SAM, the resulting perovskite solar cell exhibits striking improvements to the reach the highest efficiency of 18.8%, which constitutes an ∼10% enhancement compared to those without SAMs. Our work highlights the importance of chemical interactions at perovskite/electrode interfaces and paves the way for further optimizing performances of perovskite solar cells.

Trapped spoof surface plasmons with structured defects in textured closed surfaces.

We demonstrate that a defect unit in periodic textured closed surfaces is able to trap spoof surface plasmons (SPs) into a deep subwavelength scale. The resonant frequency of a trapped spoof SP can be tuned freely by properly tailoring the dimension of the defect unit. By introducing multiple defect units with different dimensions at different positions of the textured closed surfaces, the spoof SPs with different frequencies trapped effectively at desired places are also demonstrated. In addition, we further design a graded defect structure with continuously variable dimensions to trap the spoof SPs over an ultrawide spectral band. The interval between the trapped waves on the closed surfaces can be tuned conveniently by changing the grade of the defect dimensions. The designer structures may indicate potential applications in the optical switch and storage in the microwave and terahertz frequencies.

Physical mechanism of order between electric and magnetic dipoles in spoof plasmonic structures.

It has been recently shown that a solid-textured metal cylinder can support electric and magnetic dipolar resonances simultaneously [Phys. Rev. X4, 021003 (2014)PRXHAE2160-330810.1103/PhysRevX.4.021003] which are almost degenerate in a two-dimensional (2-D) structure and non-degenerate in a three-dimensional (3-D) structure, and with the magnetic dipole appearing at higher frequency. They are described as spoof localized plasmonic modes analogous to localized plasmonic resonances in optical frequencies. Here, we consider a hollow metal cylinder corrugated by periodic cut-through slits. Our results indicate that the magnetic dipole can be separated from the electric dipole in a 2-D structure, and magnetic dipolar resonance appears at lower frequency, rather than electric resonance in both 2-D and 3-D structures. In order to clarify the physical mechanism behind the abnormal phenomenon, we study the influence of the core material on the electric- and magnetic-dipole modes based on theoretical analysis and numerical simulation. It is discovered that there is a threshold of an imaginary part of permittivity for switching the order between electric and magnetic dipoles. These results may provide fundamental understanding and physical insight for spoof plasmonic modes supported in designer structures.